Pinnipeds exhibit a wide range of lactation strategies that vary from just a few days to nearly three years in duration. Phocids have a relatively short, intense nursing period culminating with weaning after just a few days or weeks, while dependent otariids generally take several months of consuming a combined milk and solid food diet before being completely independent. The transition to nutritional independence can be particularly challenging for newly weaned pups, which must adjust to behavioral, physiological and nutritional changes as a milk diet is replaced with solid food. An interruption in energy resources during this formative stage could result in a prioritization away from growth, maintenance, or activity resulting in suboptimal development. Three groups of ex situ California sea lion (Zalophus californianus) pups were examined during the initial period of independence after they were weaned at approximately five, seven, and nine months of age. Absolute growth rates of pups were calculated and changes in body composition were estimated using blubber depth measurements and deuterium oxide dilution to determine if weaning age had an effect on subsequent pup development and growth. Blood urea nitrogen and blood glucose levels were observed for their response to changes in body condition, while thyroid hormone levels in the blood were examined as a possible nutritional stress indicator during the pup's transition to solid food. When compared to in situ pups, the 5 month old pups in the present study had significantly greater body mass (39.6 ± 1.6 kg, p < 0.01), axillary girth (85.3 ± 2.9 cm, p < 0.01), and axillary blubber depth (2.3 ± 0.1 cm, p < 0.01) compared to 5 month old in situ pups (26.6 ± 5.2 kg / 70.6 ± 5.34 cm / 1.5 ± 0.2 cm). Nine month old ex situ pups had significantly greater axillary blubber depth (3.7 ± 0.9 cm, p < 0.01) and total body lipid percentage (24.9 ± 4.7%, p= 0.01) than in situ pups (1.5 ± 0.2 cm / 17.1 ± 4.9%). Although all pups in the present study survived the transition to solid food, there were apparent differences in how the different age groups responded physiologically. The five month old pups began the switch to solid food with the lowest overall blubber depth (2.6 ± 0.9 cm) and experienced the greatest change in body mass (-8.5 ± 1.6 kg) and composition while taking the longest to begin physiological recovery (31.7 ± 1.2 d). In contrast, the 9 month old pups entered the transition with more energy reserves (24.9 ± 4.7% TBL), began consuming solid food sooner (16.3 ± 0.6 d), and were able to utilize reserves more efficiently to minimize loss and promote faster growth.

Background: There is sound evidence that the hypothalamic-pituitary-thyroid axis plays a role in mood regulation. Alterations in this axis, particularly low triiodothyronine syndrome, are a common neuroendocrine adaptation to semi-starvation in patients with anorexia nervosa (AN), who also frequently suffer from co-existing depressive symptoms. We therefore aimed to investigate the associations between pituitary-thyroid function and psychopathology, in particular depressive symptoms, at different stages of AN using a combined cross-sectional and longitudinal study design. Methods: Pituitary-thyroid status (FT3, free triiodothyronine; FT4, free thyroxine; conversion ratio FT3/FT4; TSH, thyroid-stimulating hormone) was assessed in 77 young acutely underweight females with AN (acAN) and in 55 long-term weight-recovered individuals with former AN (recAN) in a cross-sectional comparison to 122 healthy controls (HC). Further, pituitary-thyroid status of 48 acAN was reassessed after short-term weight-restoration. We performed correlation analyses of pituitary-thyroid parameters with self-reported measures of psychopathology. Results: AcAN showed significantly lower FT3, FT4, FT3/FT4 ratio, and TSH levels compared to HC. Pituitary-thyroid alterations were partly reversed after short-term weight-restoration. RecAN still had lower FT3 concentrations than HC. Lower FT3 concentrations and FT3/FT4 ratios were associated with more severe depressive symptoms in acAN, occurring prominently in cases of manifest low triiodothyronine syndrome. Longitudinally increasing FT3/FT4 ratios (change scores) were inversely correlated with depressive and general psychiatric symptoms after short-term weight-restoration. Conclusions: Our results suggest a potential modulation of the severity of depressive symptoms by temporarily decreased FT3 concentrations and inhibited thyroid hormone conversion (FT3/FT4 ratios) in acutely underweight AN. Associations between conversion ratios FT3/FT4 and psychopathology seem to persist across short-term weight-restoration. The findings of our study might have relevant clinical implications, ranging from thyroid monitoring to experimental low-dose thyroid hormone supplementation in certain patients with AN showing severe psychiatric impairment and overt thyroid hormone alterations.

Os hormônios tireoidianos (HTs) promovem suas ações através de mecanismos genômicos, porém, há inúmeras evidências de que o HT também promove efeitos que ocorrem em curto espaço de tempo (poucos minutos), e que independem de, as quais são conhecidas como ações não genômicas ou extranucleares. É sabido que, na insuficiência cardíaca ocorre uma menor expressão dos receptores nucleares de T3, o que reduz em muito os efeitos cardioestimulantes deste hormônio, sendo muito vantajoso numa situação de contenção energética. Assim, o presente estudo visa avaliar o efeito agudo (não genômico) da administração de T3 sobre a translocação e expressão do GLUT4, e de proteínas-chave da atividade cardíaca, como GLUT1, Mb, SERCa2a, <font face=\"Symbol\">&#945; e <font face=\"Symbol\">b miosina, em: (1) ratos submetidos ou não à insuficiência cardíaca através de cirurgia de estenose aórtica, bem como em (2) cultura primária de cardiomiócitos neonatos e adultos. Nos modelos in vivo, observamos que, após 30 min da administração do T3 no grupo portador de ICC, há um aumento da expressão do mRNA do GLUT1, GLUT4 e Mb e da proteina GLUT1 e GLUT4. Quanto aos genes relacionados à função cardíaca, Atp2a2, Myh6 e Myh7, o tratamento com T3 por 30 min nos ratos portadores de ICC promoveu redução do conteúdo de mRNA dos três genes, bem como da proteína da beta MHC. O conteúdo de SERCa2a e da alfa MHC não se alterou em 30 min, mas aumentou após o tratamento com T3 por 60 min. No modelo in vitro de cardiomiócitos de neonatos, tivemos evidências de modulação do conteúdo de mRNA e proteínas, após 30 e 45 min, após a adição de T3 em diferentes doses (10-9 a 10-6 M). Quando avaliamos o efeito do T3 sobre o conteúdo de mRNA nos cardiomiócitos de adultos em cultura, também observamos uma resposta aleatória, não dependente de dose. O conjunto desses resultados aponta para a existência de um controle pós-transcricional do T3 sobre a expressão dos genes alvo desse estudo, podendo induzir uma melhora na função cardíaca na vigência de uma ICC, uma vez que essas ações são rapidamente desencadeadas e são fugazes, impedindo que os efeitos cardioestimulantes persistam, o que poderia ser deletério. / Through nuclear actions, thyroid hormones (TH) control the expression of several cardiac genes, but there are several evidences that TH also promotes effects that occur in a short time (few minutes), and which are independent of its interaction with specific nuclear receptors attached to the TH-responsive elements, known as non-genomic or extranuclear actions. In heart failure, there are a lower expression of nuclear T3 receptors, which reduce the cardiostimulating effects of the hormone, which is extremely advantageous in an energy contention. Thus, this study aims to evaluate the acute (nongenomic) administration of T3 on the expression and translocation of GLUT4, and key proteins of the cardiac activity, such as GLUT1, Mb, SERCa2a, <font face=\"Symbol\">&#945; and <font face=\"Symbol\">b myosin in: ( 1) rats with or without heart failure after aortic stenosis surgery, as well as (2) primary cultured cardiomyocytes neonates and adults. In the vivo model, after 30 min of the administration of T3 in the group with CHF, there is an increased in the mRNA expression in GLUT1, GLUT4 and Mb. Their proteins had an increase after 30 min (GLUT1 and GLUT4) and after 60 min (Mb). As for genes related to cardiac function, Atp2a2, Myh6 and MYH7, we observed that, the treatment with T3 for 30 min in rats with CHF promoted a decrease of the mRNA of three genes as well as the beta MHC protein. The content of alpha-MHC and SERCa2a did not change in 30 min, but increased after T3 treatment for 60 min. In the in vitro model of neonatal cardiomyocytes, we had evidence of modulation of mRNA and protein content after 30 and 45 min after the addition of T3 in different doses (from 10-9 to 10-6 M). When evaluating the effect of T3 on the mRNA content in adult cardiomyocytes in culture, we also observed a random response, not dependent on dose. All the data obtained so far points to the existence of a post-transcriptional control of T3 on the expression of target genes of this study, which could induce an improvement in cardiac function in the presence of an CHF, since these actions are elicited and fleeting, preventing cardiostimulating effects persist, which could be deleterious.

It is generally thought that in amphibians, thyroid hormones (THs) regulate metamorphosis, while sex steroids (estrogens and androgens) regulate gonadal differentiation. However, inhibition of TH synthesis in frogs alters gonadal differentiation, suggesting instead that these two endocrine axes interact during development. Specifically, THs may be involved in male development, while estrogens may inhibit tadpole metamorphosis. However, we do not currently know the mechanisms that account for these interactions, let alone how such mechanisms may differ between species. To develop and test new hypotheses on the roles of sex steroids and THs, I first examined transcriptional profiles (mRNA) of enzymes and receptors related to sex steroids and THs during embryogenesis and metamorphosis in Silurana tropicalis. Tadpoles were exposed to either an estrogen synthesis inhibitor (fadrozole) or TH (triiodothyronine, T3) during early larval or tadpole development. Acute exposures of S. tropicalis to fadrozole or T3 during early development resulted in increased expression of androgen- and TH-related genes in whole body larvae, while chronic exposure to fadrozole during metamorphosis affected gonadal differentiation but did not affect tadpole development. On the other hand, acute exposure to T3 during metamorphosis increased the expression of androgen-related transcripts both in the brain and gonad. In S. tropicalis, the results suggested that cross-talk is primarily in one direction (i.e., effect of THs on the reproductive axis) with a strong relationship between TH and androgen status. Lastly, I established developmental transcript profiles and investigated T3 regulation of brain and gonad transcripts in Engystomops pustulosus. I then compared these results with S. tropicalis and an earlier study in Lithobates pipiens. While each species developed with similar profiles, they differed in their response to T3. Exposure to T3 resulted in either an increase in androgen-related genes (S. tropicalis) or a decrease in estrogen-related genes (E. pustulosus and L. pipiens). In conclusion, these data demonstrated that cross-talk mechanisms differ among these three evolutionary separate species, but in all cases, T3 appears to affect the balance of sex steroids, stimulating the androgen system and providing potential mechanisms of the masculinising effects of THs. These results will contribute to understanding the mechanisms of hormone interactions and their evolutionary basis in frogs.

It is generally thought that in amphibians, thyroid hormones (THs) regulate metamorphosis, while sex steroids (estrogens and androgens) regulate gonadal differentiation. However, inhibition of TH synthesis in frogs alters gonadal differentiation, suggesting instead that these two endocrine axes interact during development. Specifically, THs may be involved in male development, while estrogens may inhibit tadpole metamorphosis. However, we do not currently know the mechanisms that account for these interactions, let alone how such mechanisms may differ between species. To develop and test new hypotheses on the roles of sex steroids and THs, I first examined transcriptional profiles (mRNA) of enzymes and receptors related to sex steroids and THs during embryogenesis and metamorphosis in Silurana tropicalis. Tadpoles were exposed to either an estrogen synthesis inhibitor (fadrozole) or TH (triiodothyronine, T3) during early larval or tadpole development. Acute exposures of S. tropicalis to fadrozole or T3 during early development resulted in increased expression of androgen- and TH-related genes in whole body larvae, while chronic exposure to fadrozole during metamorphosis affected gonadal differentiation but did not affect tadpole development. On the other hand, acute exposure to T3 during metamorphosis increased the expression of androgen-related transcripts both in the brain and gonad. In S. tropicalis, the results suggested that cross-talk is primarily in one direction (i.e., effect of THs on the reproductive axis) with a strong relationship between TH and androgen status. Lastly, I established developmental transcript profiles and investigated T3 regulation of brain and gonad transcripts in Engystomops pustulosus. I then compared these results with S. tropicalis and an earlier study in Lithobates pipiens. While each species developed with similar profiles, they differed in their response to T3. Exposure to T3 resulted in either an increase in androgen-related genes (S. tropicalis) or a decrease in estrogen-related genes (E. pustulosus and L. pipiens). In conclusion, these data demonstrated that cross-talk mechanisms differ among these three evolutionary separate species, but in all cases, T3 appears to affect the balance of sex steroids, stimulating the androgen system and providing potential mechanisms of the masculinising effects of THs. These results will contribute to understanding the mechanisms of hormone interactions and their evolutionary basis in frogs.

It is generally thought that in amphibians, thyroid hormones (THs) regulate metamorphosis, while sex steroids (estrogens and androgens) regulate gonadal differentiation. However, inhibition of TH synthesis in frogs alters gonadal differentiation, suggesting instead that these two endocrine axes interact during development. Specifically, THs may be involved in male development, while estrogens may inhibit tadpole metamorphosis. However, we do not currently know the mechanisms that account for these interactions, let alone how such mechanisms may differ between species. To develop and test new hypotheses on the roles of sex steroids and THs, I first examined transcriptional profiles (mRNA) of enzymes and receptors related to sex steroids and THs during embryogenesis and metamorphosis in Silurana tropicalis. Tadpoles were exposed to either an estrogen synthesis inhibitor (fadrozole) or TH (triiodothyronine, T3) during early larval or tadpole development. Acute exposures of S. tropicalis to fadrozole or T3 during early development resulted in increased expression of androgen- and TH-related genes in whole body larvae, while chronic exposure to fadrozole during metamorphosis affected gonadal differentiation but did not affect tadpole development. On the other hand, acute exposure to T3 during metamorphosis increased the expression of androgen-related transcripts both in the brain and gonad. In S. tropicalis, the results suggested that cross-talk is primarily in one direction (i.e., effect of THs on the reproductive axis) with a strong relationship between TH and androgen status. Lastly, I established developmental transcript profiles and investigated T3 regulation of brain and gonad transcripts in Engystomops pustulosus. I then compared these results with S. tropicalis and an earlier study in Lithobates pipiens. While each species developed with similar profiles, they differed in their response to T3. Exposure to T3 resulted in either an increase in androgen-related genes (S. tropicalis) or a decrease in estrogen-related genes (E. pustulosus and L. pipiens). In conclusion, these data demonstrated that cross-talk mechanisms differ among these three evolutionary separate species, but in all cases, T3 appears to affect the balance of sex steroids, stimulating the androgen system and providing potential mechanisms of the masculinising effects of THs. These results will contribute to understanding the mechanisms of hormone interactions and their evolutionary basis in frogs.

Os hormônios tireoidianos (HTs) promovem suas ações através de mecanismos genômicos, porém, há inúmeras evidências de que o HT também promove efeitos que ocorrem em curto espaço de tempo (poucos minutos), e que independem de, as quais são conhecidas como ações não genômicas ou extranucleares. É sabido que, na insuficiência cardíaca ocorre uma menor expressão dos receptores nucleares de T3, o que reduz em muito os efeitos cardioestimulantes deste hormônio, sendo muito vantajoso numa situação de contenção energética. Assim, o presente estudo visa avaliar o efeito agudo (não genômico) da administração de T3 sobre a translocação e expressão do GLUT4, e de proteínas-chave da atividade cardíaca, como GLUT1, Mb, SERCa2a, <font face=\"Symbol\">&#945; e <font face=\"Symbol\">b miosina, em: (1) ratos submetidos ou não à insuficiência cardíaca através de cirurgia de estenose aórtica, bem como em (2) cultura primária de cardiomiócitos neonatos e adultos. Nos modelos in vivo, observamos que, após 30 min da administração do T3 no grupo portador de ICC, há um aumento da expressão do mRNA do GLUT1, GLUT4 e Mb e da proteina GLUT1 e GLUT4. Quanto aos genes relacionados à função cardíaca, Atp2a2, Myh6 e Myh7, o tratamento com T3 por 30 min nos ratos portadores de ICC promoveu redução do conteúdo de mRNA dos três genes, bem como da proteína da beta MHC. O conteúdo de SERCa2a e da alfa MHC não se alterou em 30 min, mas aumentou após o tratamento com T3 por 60 min. No modelo in vitro de cardiomiócitos de neonatos, tivemos evidências de modulação do conteúdo de mRNA e proteínas, após 30 e 45 min, após a adição de T3 em diferentes doses (10-9 a 10-6 M). Quando avaliamos o efeito do T3 sobre o conteúdo de mRNA nos cardiomiócitos de adultos em cultura, também observamos uma resposta aleatória, não dependente de dose. O conjunto desses resultados aponta para a existência de um controle pós-transcricional do T3 sobre a expressão dos genes alvo desse estudo, podendo induzir uma melhora na função cardíaca na vigência de uma ICC, uma vez que essas ações são rapidamente desencadeadas e são fugazes, impedindo que os efeitos cardioestimulantes persistam, o que poderia ser deletério. / Through nuclear actions, thyroid hormones (TH) control the expression of several cardiac genes, but there are several evidences that TH also promotes effects that occur in a short time (few minutes), and which are independent of its interaction with specific nuclear receptors attached to the TH-responsive elements, known as non-genomic or extranuclear actions. In heart failure, there are a lower expression of nuclear T3 receptors, which reduce the cardiostimulating effects of the hormone, which is extremely advantageous in an energy contention. Thus, this study aims to evaluate the acute (nongenomic) administration of T3 on the expression and translocation of GLUT4, and key proteins of the cardiac activity, such as GLUT1, Mb, SERCa2a, <font face=\"Symbol\">&#945; and <font face=\"Symbol\">b myosin in: ( 1) rats with or without heart failure after aortic stenosis surgery, as well as (2) primary cultured cardiomyocytes neonates and adults. In the vivo model, after 30 min of the administration of T3 in the group with CHF, there is an increased in the mRNA expression in GLUT1, GLUT4 and Mb. Their proteins had an increase after 30 min (GLUT1 and GLUT4) and after 60 min (Mb). As for genes related to cardiac function, Atp2a2, Myh6 and MYH7, we observed that, the treatment with T3 for 30 min in rats with CHF promoted a decrease of the mRNA of three genes as well as the beta MHC protein. The content of alpha-MHC and SERCa2a did not change in 30 min, but increased after T3 treatment for 60 min. In the in vitro model of neonatal cardiomyocytes, we had evidence of modulation of mRNA and protein content after 30 and 45 min after the addition of T3 in different doses (from 10-9 to 10-6 M). When evaluating the effect of T3 on the mRNA content in adult cardiomyocytes in culture, we also observed a random response, not dependent on dose. All the data obtained so far points to the existence of a post-transcriptional control of T3 on the expression of target genes of this study, which could induce an improvement in cardiac function in the presence of an CHF, since these actions are elicited and fleeting, preventing cardiostimulating effects persist, which could be deleterious.

It is generally thought that in amphibians, thyroid hormones (THs) regulate metamorphosis, while sex steroids (estrogens and androgens) regulate gonadal differentiation. However, inhibition of TH synthesis in frogs alters gonadal differentiation, suggesting instead that these two endocrine axes interact during development. Specifically, THs may be involved in male development, while estrogens may inhibit tadpole metamorphosis. However, we do not currently know the mechanisms that account for these interactions, let alone how such mechanisms may differ between species. To develop and test new hypotheses on the roles of sex steroids and THs, I first examined transcriptional profiles (mRNA) of enzymes and receptors related to sex steroids and THs during embryogenesis and metamorphosis in Silurana tropicalis. Tadpoles were exposed to either an estrogen synthesis inhibitor (fadrozole) or TH (triiodothyronine, T3) during early larval or tadpole development. Acute exposures of S. tropicalis to fadrozole or T3 during early development resulted in increased expression of androgen- and TH-related genes in whole body larvae, while chronic exposure to fadrozole during metamorphosis affected gonadal differentiation but did not affect tadpole development. On the other hand, acute exposure to T3 during metamorphosis increased the expression of androgen-related transcripts both in the brain and gonad. In S. tropicalis, the results suggested that cross-talk is primarily in one direction (i.e., effect of THs on the reproductive axis) with a strong relationship between TH and androgen status. Lastly, I established developmental transcript profiles and investigated T3 regulation of brain and gonad transcripts in Engystomops pustulosus. I then compared these results with S. tropicalis and an earlier study in Lithobates pipiens. While each species developed with similar profiles, they differed in their response to T3. Exposure to T3 resulted in either an increase in androgen-related genes (S. tropicalis) or a decrease in estrogen-related genes (E. pustulosus and L. pipiens). In conclusion, these data demonstrated that cross-talk mechanisms differ among these three evolutionary separate species, but in all cases, T3 appears to affect the balance of sex steroids, stimulating the androgen system and providing potential mechanisms of the masculinising effects of THs. These results will contribute to understanding the mechanisms of hormone interactions and their evolutionary basis in frogs.